The Leader of the Smallpox Eradication Effort Speaks About the Virus’ Rediscovery

Those of us who write about infectious diseases faced a conundrum last week, when the news broke that 60-year-old vials containing viable smallpox virus had been found on the National Institutes of Health campus. A responsible reporter always wants to talk to the experts in any subject. But when it comes to smallpox, experts can be hard to find.

Smallpox was one of the world’s worst killers, from prehistory through the first half of the 20th century. Yet there has not been a case of the dreadful disease anywhere since 1978, so few physicians working today have seen one. The virus is supposed to exist in only two highly secure stockpiles, so few scientists do research on it. And the aggressive campaign that chased the disease from the globe — the only human infection for which that claim can be made — ended 34 years ago. Many of the men and women who led it are in retirement, and a number have died.

Fortunately, the physician who headed that international campaign — 85-year-old Donald Ainslie Henderson, universally known as D.A. — is still working in public health, as a distinguished scholar at the bioterrorism-focused Center for Health Security of the University of Pittsburgh Medical Center. Henderson literally wrote the book on smallpox — twice, in fact: He co-authored the World Health Organization’s definitive 1,500-page reference, Smallpox and its Eradication (known in public health as the Red Book), and in 2009 wrote a personal reminiscence of the global battle, Smallpox: The Death of a Disease. Just last month, he published a lengthy, closely argued essay in the journal he co-edits, Biosecurity and Bioterrorism, urging the WHO to finally consent to destroying the last stocks of smallpox virus. (A decision the international agency declined to take; instead, for the sixth time in a row, it postponed a vote on destruction in favor of more study.) There are only a few people working in public health — not just in the United States, but in the world — who possess equivalent knowledge of smallpox, its eradication, and the persistent fears afterward that it could be used as a bioterror agent.

Last week, I talked to Henderson about the live-virus discovery and whether it will affect calls for all stocks of smallpox to be destroyed. He had some surprising things to say, particularly about the availability of smallpox vaccine. I edited our conversation for clarity and length.

Maryn McKenna: Were you surprised at the find?

D.A. Henderson: Yes, in a way, I was. At the time, we thought we had the virus properly corralled in (Novosibirsk and Atlanta), and had affidavits from each of the remaining countries saying that they did not have any. They searched their laboratories and could find no evidence of smallpox.

But I think if one knows the practice of virologists, microbiologists, it’s very common for them to get an isolate, put it into some sort of container, freeze it. Having been a dean, I know. Some of the containers will have lost their labels, and some have not been looked at for a very long time. So we had to face the fact that there’s no way that we’re going to be absolutely certain that there was no smallpox anywhere, no matter what we did.

MM: This is not the first time this has happened, right? I have heard once in California, and once in London.

DAH: Indeed. In the two instances concerned, it was a discovery of great embarrassment. They thought they did not have smallpox virus, and they discovered it and promptly autoclaved it. It was something that really never went in the papers. The scenario that I just gave you, about people putting things in deep freezers and forgetting them, that is the same thing that happened in London and in California.

MM: So, does this change your point of view at all about retention versus destruction of the remaining stocks?

DAH: No, not at all. I think it’s really desirable we go ahead and destroy it. What are we going to use the smallpox virus for? The justification that you hear for retaining it at this point is to develop a better vaccine and also to develop antiviral products. But we’ve spent maybe $500 million on that goal so far. We have better uses for our money.

MM: What do you think of the contention that we should hang onto smallpox because its effect on the human immune system is so unique that we should study it further?

DAH: Well, it’s hard to study the human impact without human infection, which no one would want. There wasn’t much serological work done at the time we had smallpox, because we didn’t have the tools at that time. So we don’t really know as much about the human response as we might have.

But a great number of specimens from different strains of the smallpox virus have now been sequenced, and broken into fragments and incorporated into E. coli. Those could be studied. It’s not the same as studying the whole virus, that’s for sure, but it’s pretty hard to see how we could use the virus as it is.

MM: So the discovery of these vials, and the possibility there might be more somewhere, has not changed your mind about destroying the existing smallpox stocks?

DAH: No. One reason that many of us feel this would be desirable is that it would make it clear that any one who possesses smallpox virus beyond the destruction date would be de facto guilty of crimes against humanity. That is the message that destroying it would send.

MM: I’m looking at your incredibly well-timed piece in Biosecurity and Bioterrorism. You argue that by continuing to pursue smallpox vaccine research and antivirals for treatment of any future smallpox case, we’ve chosen the wrong priorities in public health spending.

DAH: Exactly. We have the present vaccine, the ACAM2000, which we have 220 million doses of. It’s very stable and it has held up in potency very well. That’s a derivative of the vaccine that we used, I want to say exclusively, from about 1920 until 1985. It was called Dryvax. There are complications that the vaccine does cause. This has been a subject of some considerable anxiety.

So we have a vaccine and no reason now to believe it’s ever going to be used. We hope it would never be used. Why are we struggling to make a less reactogenic vaccine? What we really should be concerned about would be: Do we have a vaccine that we know will protect? We do. If we come up with something else, how do we know it’ll protect? We don’t, because we can’t test it.

My feeling is we’re wasting our money. Instead of putting money into preparedness at state and local health departments, and communication systems, and the ability to respond quickly to epidemics, we’re spending money on developing a vaccine and an antiviral product which we hope we’ll never use.

MM: About the US vaccine stockpile: 220 million doses is less than the US population. Do we have enough?

DAH: We have enough vaccine for the U.S. There’s no anticipation by anybody that we’ll ever go into a mass vaccination program again. If you do have a vaccine, you can stop it from spreading, and we saw that in the eradication program even under really severe conditions.

What we’re lacking, as we look at it, is globally. There probably are not more than 300 million doses of smallpox vaccine, in total, throughout the whole of the world.

We recommended early on to have at least one manufacturing facility in the U.S. on a standby basis, producing a small amount of vaccine every year, which could be greatly hiked up if you had to. That has not been achieved. There is one facility that is supposed to open in the US, but it has been very slow to set up, and may not open until the end of next year.

The facility from which the 220 million doses came was from a company in Austria. It was a converted influenza-vaccine production facility, and afterward it went back to making other things. In the world right now, we just have one manufacturing facility for smallpox vaccine, and that is in Japan. That’s not good.